This application proposes to continue the overall research direction established during the past project period and to continue the current administrative structure as a combined adult and pediatric unit, which has been a successfull operation over the past nine years. The Program Director is responsible for the day-to-day operation of the entire Center, and the Associate Director is primarily responsible for supervision of pediatric patients and protocols. The Core Lab, under direction of the Assistant Program Director, will continue to provide assays of gonadotropins and cortisol as well as DNA processing, all required by a number of investigators. Increased patient care, dietary and core laboratory personnel are requested to adequately support the several high intensity protocols in progress as well as those anticipated in the tuture. Support of the statistical unit at its current level is requested to provide consultation for study design, protocol review and data analysis. Current and planned educational initiatives will provide training in the GCRC for medical students, housestaff, fellows and junior faculty. CAP and MCAP awardees will also benefit from the educational programs and will continue to receive guidance in the planning, conduct and analysis of their research. Increased volume of research activity is anticipated primarily from outpatient protocols, with stable use of inpatient facilities. Based upon current programs and those proposed, we anticipate a greater diversity of research projects from the departments of Medicine, Pediatrics, Psychiatry, Obstetrics and Gynecology, Clinical Pharmacology, Anesthesiology, Surgery and Biochemistry and Molecular Biology. Among the programs in adults and children are: diabetes (beta cell function, genetics of non-insulin dependent diabetes mellitus, prevention trial in insulin-dependent diabetes mellitus), other areas of endocrinology (thyroid hormone resistance, pubertal and growth disorders, regulation of circadian rhythms, osteoporosis), psychiatry (determinants of drug preference, hormones and drug response), oncology and clinical pharmacology (benzylguanine in advanced cancer, 5-fluorouracil metabolism), nephrology (pathogenesis of calcium stone formers, dietary acid regulation of calcium balance), gynecology (genetics of polycystic ovary syndrome, ovarian steroids and insulin resistance), pulmonary (genetic studies and airway eosinophil function in asthma), anesthesiology (drugs for ambulatory surgery), gastroenterology and nutrition (calcium metabolism and genetic mapping in ulcerative colitis and Crohn's disease) and rheumatology (pentostatin in rheumatoid arthritis, bone metabolism in juvenile rheumatoid arthritis).